Proprotein convertase subtilisin/kexin type 9 related familial hypercholesterolaemia

Abstract

Gain-of-function proprotein convertase subtilisin/kexin type 9 (PCSK9) mutations are an uncommon cause of familial hypercholesterolaemia (FH) with a reported frequency of less than 2% in patients with FH in the United Kingdom. We have found a high prevalence of this genotype in our patients with FH in northwest England. Out of 48 patients with possible, probable or definite FH screened for FH associated mutations in our clinic, five (10%) were found to have the same gain-of-function mutation in PCSK9. We present clinical details and lipid results before and during treatment on eight patients with this mutation and compare these findings with those in nine patients with FH due to low-density lipoprotein receptor (LDLR) gene mutations. Gain-of-function mutations in PCSK9 result in a more severe clinical phenotype with a higher prevalence of early onset cardiovascular disease. The more severe hypercholesterolaemia is refractory to treatment compared with LDLR related FH.